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Effects of the nanocomposite and its components (magnetic fluid, cisplatin) on the level of endogenous iron exchange and the key links of genetic and epigenetic regulation of apoptotic program of sensitive and resistant MCF-7 cells were examined. We showed genetic and epigenetic mechanisms of action of nanocomposite of magnetic fluid and cisplatin. Nanocomposite caused elevation of number of cells in apoptosis in sensitive and especially resistant MCF-7 cells compared to cisplatin alone. It was proved that impact of nanocomposite on MCF-7/S and MCF-7/DDP cells caused more significant changes in expression of apoptosis regulators p53, Bcl-2 and Bax. We also suggested that changes in endogenous iron homeostasis and activation of free radical processes caused significant impact on apoptosis. Those changes included changes in methylation and expression of transferrin, its receptors, ferritin heavy and light chains (predominantly in resistant cell line), which caused activation of free radical synthesis and development of oxidative stress. We also showed that nanocomposite impact resulted into significant changes in expression of miRNA-34a and miRNA-200b, which regulated apoptosis, cell adhesion, invasion and activity of ferritin heavy chains gene. Thus, use of nanocomposite containing cisplatin and ferromagnetic as exogenous source of Fe ions caused changes of endogenous iron levels in sensitive and resistant cells allowing to increase specific activity of cytostatics and overcome factors, which promoted MDR development. Pharmacocorrection of endogenous iron metabolism allowed increasing antitumor activity of cisplatin and overcoming drug resistance.

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The aim of the investigations was to evaluate benefits of the directed transport system-a nanocomposite, based on cisplatin and magnetite combined with local action of constant magnetic field on the tumor, in experiments in vivo in animals with transplantable Guerin carcinoma. Animals were divided into 5 groups according to the type of agent. We showed that nanocomposite in combination with static magnetic field exercises more prominent anti-tumor activity than cisplatin alone. It should be noted that regardless of the therapeutic agent, in Guerin carcinoma we observed cytotoxic effects of the same profile type. However, the degree of these changes' manifestation depended on the type of applied factor. The most prominent manifestations of pathomorphosis in tumor tissue were observed under combined action of nanocompositte and static magnetic field. Comparative analysis of the results of using as anti-tumor drugs cisplatin; cisplatin in combination with tumor exposure to static magnetic field; nanocomposite, and combination of nanocomposite with static magnetic field, showed that the most pronounced cytotoxic effect in tumors was achieved with nanosystem of targeted transport. Comparison analysis of nanocomposite accumulation in tumors of animals received only nanocomposite with the results of its accumulation after magnetic field local tumor exposure showed that the static magnetic field results in greater NC inflow to the tumor. Nanocomposite administration resulted in changes of both total lipids and phospholipids compositions in tumor tissue. At the same time, phospholipids composition in the liver of animals treated with nanocomposite did not change in fact. The administration of nanocomposite did not affect the blood total indexes, but increased serum creatinine level. Lack of significant damaging effect of nanocomposite on total and biochemical blood indexes, lipid composition of hepatocytes indicates its low toxicity and suggests the possibility of its use as a vector in nanosystems for anti-tumor drugs delivery. * Significantly (P < 0.05) higher compared to control.